Conervation of OFD1 Protein Motifs Implications for Discovery of Novel Interactors

OFD1 is a protein involved in many cellular processes, including cilia biogenesis, mitotic spindle assembly, translation, autophagy and repair of double-strand DNA breaks. Despite many potential interactors identified in high-throughput studies, only few have been directly confirmed and their binding sites identified.<br>We performed analysis of the evolutionary conservation of OFD1 sequence in 80 Tetrapoda, 144 Vertebrata or 26 Animalia species, and identified 59 protein-binding motifs localized in the OFD1 regions conserved in various clades. Our results indicate that OFD1 is tightly regulated by posttranslational modifications (PTM) and may also regulate other proteins: it contains 14 potential PTM sites targeted by at least eight protein kinases, 7 motifs bound by proteins recognizing phosphorylated aa residues, as well as a binding site for phosphatase 2A. Moreover, OFD1 harbors both, a motif that enables its phosphorylation by mitogen-activated protein kinases (MAPKs), and a docking site specific for these proteins.<b> </b>Generally, our results suggest that OFD1 forms a scaffold for interaction with many proteins and is tightly regulated by post-translational modifications and ligands. Future research on OFD1 should focus on regulation of OFD1 function and localization.